Cinacalcet hydrochloride.: Treatment of hyperparathyroidism

Hyperparathyroidism is characterized by high levels of circulating calcium due to an increased secretion of parathyroid hormone (PTH) by one or more of the parathyroid glands. It is estimated that 28 out of every 100,000 people in the U.S. will develop this disorder. A standard treatment for hyperparathyroidism is surgical removal of the affected gland(s). However, pharmacological intervention with vitamin ID analogs of calcimimetics is an option for those patients with mild cases or secondary hyperparathyroidism. The extracellular calcium sensing receptor (CaR), a low affinity G-protein-coupled receptor, is found in high levels on the surface of parathyroid cells, where in response to small changes in extracellular calcium, they regulate secretion of PTH. The CaR is an attractive therapeutic target for the design of novel calcimimetics for the treatment of hyperparathyroidism because alterations in CaR expression are thought to be responsible for inherited forms of hypercalcemia and hyperparathyroidism, and acquired alterations in this receptor could be responsible for the pathogenesis of primary hyperparathyroidism and secondary hyperparathyroidism due to renal failure. Cinacalcet hydrochloride is a novel second-generation calcimimetic that modulates the CaR by making it more sensitive to the calcium suppressive effects on PTH secretion. It has a high oral bioavailability and has been chosen for further development as a treatment for primary and secondary hyperparathyroidism.